[Ip-health] DNDi's R&D Efforts on Sleeping Sickness Highlighted Today in the New York Times

[Ann-Marie Sevcsik]

Today in the New York Times, Don McNeil reports on the DNDi's HAT-related R=
&D efforts and also really brings the patient needs to light as well:
http://www.nytimes.com/2008/01/08/health/research/08slee.html?ref=3Dhealth

New York Times
________________________________________
January 8, 2008
Jump-Start on Slow Trek to Treatment for a Disease
By DONALD G. McNEIL Jr.
Last month, the Bill and Melinda Gates Foundation donated $19 million to th=
e Drugs for Neglected Diseases Initiative to further one of its goals: find=
ing a new drug for African sleeping sickness.
Not that $19 million will come close to doing that. Even if a miracle cure =
is found, it will take lab work and clinical trials that could easily cost =
$100 million to prove it is really a miracle and not the Vioxx of the Afric=
an savannah.
But the gift spotlights just how tricky the search for new treatments can b=
e when the disease is fearsome but nearly forgotten because its victims are=
 poor and obscure.
The plan for sleeping sickness is a series of incremental steps, said Dr. B=
ernard P=E9coul, a former member of Doctors Without Borders who founded the=
 partnership in 2003.
A drug started from scratch might not be ready till 2020 or later. A perfec=
t one, he said, would be taken orally, would cure the disease in less than =
a week and would have no horrible side effects. But until then, even slight=
 advances in treatment will benefit victims, who now face choices familiar =
to cancer patients: the cure is so rough that the only thing worse is no cu=
re.
"Sleeping sickness" is too benign a nickname for human African trypanosomia=
sis, which is caused by a protozoan spread by biting tsetse flies. When the=
 parasites enter the brain, victims hallucinate wildly. They have been know=
n to chase neighbors with machetes, throw themselves into latrines and scre=
am with pain at the touch of water. Only at the end do they lapse into a la=
ssitude so great that they cannot eat, followed by coma and death.
About 150,000 people contract the disease each year, but 50 million people =
in 36 countries live in areas where they are at risk.
The best treatment now is eflornithine, sometimes called the resurrection d=
rug because it can pull the dying out of comas.
It is almost a miracle that eflornithine is available. It was discovered in=
 1980 at Pace University in New York. By early 2000, the last 7,500 doses i=
n the world were running out. The patentholder, a precursor of the drug mak=
er Sanofi-Aventis, abandoned it in 1995 because it had not lived up to its =
anticancer potential. Then, in late 2000, plans to make a topical form emer=
ged. It was the key ingredient in Vaniqa, a cream to prevent facial hair in=
 women.
After critics accused Sanofi-Aventis of catering to vain rich women while l=
etting poor Africans die, the company agreed to make an injectable form of =
the drug and now gives it free to the World Health Organization and Doctors=
 Without Borders.
But in rural Africa, eflornithine is very hard to use. Patients need intrav=
enous infusions four times a day for two weeks. When a "hospital" is a row =
of iron beds under a thatched roof, and the "nursing staff" is mostly relat=
ives of the sick who sleep on the floor, round-the-clock treatment is hard.=
 There might be no night nurse to insert an IV line.
For that reason, many countries do not adopt it. They still use the drug me=
larsoprol, which, Dr. P=E9coul said, "is not effective and sometimes kills.=
"
Melarsoprol, invented in the 1940s, is essentially arsenic dissolved in pro=
pylene glycol, the antifreeze ingredient. It can be given once a day for 10=
 days, which is easier on nurses. But it kills 5 percent of those who take =
it and burns survivors' veins.
Dr. P=E9coul hopes to have more countries switch to a mix of seven days of =
eflornithine twice a day - so that night nurses are not needed - plus seven=
 days of nifurtimox, an oral drug that kills protozoa but is ineffective al=
one. To do that, he hopes by next year to be able to report favorable resul=
ts from clinical trials under way at six sites in Uganda, Congo and the Con=
go Republic, and then persuade the W.H.O. to recommend the regimen.
By 2014, he hopes to have evidence that another drug, fexinidazole, is bett=
er. It can be taken orally, and in animal tests it cures even late-stage sl=
eeping sickness in the brain within two weeks. But it has not been tested o=
n humans. Phase 1 trials, small tests of its safety in humans, are to start=
 late this year.
Fexinidazole was developed by the German pharmaceutical company Hoechst, no=
w part of Sanofi-Aventis, and abandoned in the 1980s when the company gave =
up its tropical disease programs, said Els Torreele, who directs the initia=
tive's fexinidazole project. It is one of a class of drugs known as azoles,=
 like fluconazole, that work against fungi and may work against cancer.
"We tested 500 different azoles," Dr. P=E9coul said. The advantage of adopt=
ing an abandoned drug is that the former patentholder has usually done the =
chemical analyses, animal studies and, sometimes, early human trials, savin=
g millions of dollars.
The $19 million from the Gates Foundation is not for that, but to begin the=
 hunt for a completely new candidate.
Yves J. Ribeill, founder of Scynexis, a North Carolina drug company that wi=
ll receive much of the grant, said his chemists would fill legions of tiny =
test tubes with parasites swimming in calf serum, and legions more with mam=
malian tissue cells, and dose them all with thousands of molecules from che=
mical "libraries." Dr. P=E9coul's group has negotiated deals to use about 2=
0 university and drug company libraries.
After gathering "hits" - compounds that kill parasites but not cells - Scyn=
exis has to work out ways to make them into "leads," which are versions tha=
t are potent, safe and easy to make, and will "last long enough in the bloo=
d to have an effect and then disappear," Dr. Ribeill said.
Then trials begin, first in mice, then in other animals and finally in huma=
ns. Each will take years and will need further grants like the latest from =
the Gates Foundation.
"When you have a lead," Dr. P=E9coul said, "you are still far away from hav=
ing a drug."



*****************************************
Ann-Marie Sevcsik
Scientific Communications Manager
Drugs for Neglected Diseases initiative (DNDi)
Place St Gervais 1 / 1201 Geneva / Switzerland
+41=A0(0)22 906 9230/50 (office/direct); + 41(0)22 906 9231 (fax)
+41 (0)79 814 9147 (mobile)
amsevcsik@dndi.org
=A0
DNDi has just launched its first product: read more at www.actwithasaq.org
Learn more about 'Best sciences for the most neglected' at www.dndi.org
*****************************************